Cell Mechanism Discovery Key to Stopping Breast Cancer Metastasis

By The ASCO PostJanuary 15, 2014, Volume 5, Issue 1

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Researchers from Huntsman Cancer Institute at the University of Utah discovered a cellular mechanism that drives breast cancer metastasis, as well as a therapy which blocks that mechanism. The research results were recently published online in the journal Cell Reports.1

“Genetic mutations do not drive this mechanism,” said Alana Welm, PhD, Senior Author of the study, Associate Professor in the Department of Oncological Sciences, and an Investigator at Huntsman Cancer Institute. “Instead, it’s improper regulation of when genes turn on and off.”

RON Kinase

The new discovery focuses on a protein called RON kinase (RON), which signals some areas of tumor cell DNA to become active. Normally, RON operates mostly during embryonic development and is not highly expressed in healthy adults. But in about 50% of breast cancer cases, RON becomes reexpressed and reprograms genes responsible for metastasis, making them active.

“If there’s an entire program in the tumor cell that’s important for metastasis, blocking one small part of that program, for example, the action of a single gene, will probably not be an effective strategy,” said Dr. Welm. “But if you could find a way to turn off the entire program, you’re more likely to have the desired effect. We found that inhibiting RON turns off the entire metastasis program in these tumor cells.

Future work will include investigating the potential of detecting the RON-dependent program in tumor cells as a way to identify patients that are more likely to develop metastases and as a predictor of therapeutic response to drugs that inhibit RON. ■

The work was funded by the DOD Breast Cancer Research Program Era of Hope Scholar Award, a Susan G. Komen for the Cure Career Catalyst Award, and Huntsman Cancer Foundation. Research reported in this publication utilized HCI’s Microarray and Genomic Analysis Shared Resource and was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA042014.